León Valdivieso

University of Buenos Aires, Buenos Aires, Buenos Aires F.D., Argentina

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Publications (38)

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    [Show abstract] [Hide abstract] ABSTRACT: Critical limb ischemia complicates peripheral artery disease leading to tissue damage and amputation. We hypothesized that modifying adipose stromal cells (ASCs) to overexpress human vascular endothelial growth factor 165 (VEGF) would limit ischemic muscle damage to a larger extent than nonmodified ASCs. Rabbits with critical hindlimb ischemia were injected with allogeneic abdominal fat-derived ASCs transfected with plasmid-VEGF165 (ASCs-VEGF; n=10). Additional rabbits received nontransfected ASCs (ASCs; n=10) or vehicle (placebo; n=10). One month later, ASCs-VEGF rabbits exhibited significantly higher density of angiographically visible collaterals and capillaries versus placebo (both P<0.05) but not versus ASCs (both P=NS). Arteriolar density, however, was increased in both ASCs and ASCs-VEGF groups (both P<0.05 versus placebo). ASCs-VEGF and ASCs showed comparable post-treatment improvements in Doppler-assessed peak systolic velocity, blood pressure ratio, and resistance index. Ischemic lesions were found in 40% of the muscle samples in the placebo group, 19% in the ASCs-VEGF group, and 17% in the ASCs groups (both P<0.05 versus placebo, Fisher test). In a rabbit model of critical limb ischemia, intramuscular injection of ASCs genetically modified to overexpress VEGF increase angiographically visible collaterals and capillary density. However, both modified and nonmodified ASCs increase arteriolar density to a similar extent and afford equal protection against ischemia-induced muscle lesions. These results indicate that modifying ASCs to overexpress VEGF does not enhance the protective effect of ASCs, and that arteriolar proliferation plays a pivotal role in limiting the irreversible tissue damage of critical limb ischemia. © 2014 American Heart Association, Inc.
    Full-text Article · Nov 2014 · Arteriosclerosis Thrombosis and Vascular Biology
  • [Show abstract] [Hide abstract] ABSTRACT: Thromboembolic pulmonary disease is challenging for physicians when diagnosed in acute, sub-acute and chronic clinical patients, not only due to its morbi-mortality, but also because of its complex therapeutic management. Severity of the acute condition and potential commitment of right ventricular systolic function require therapeutic strategies, sometimes combined, in order to change the disease's course, optimizing patient survival. Pharmacological and mechanical thrombolysis are useful therapeutic tools for patients suffering from severe acute pulmonary embolism. This study refers to a young woman who developed a sub-massive pulmonary embolism, of sub-acute onset. She underwent the combined sequential therapeutic strategy of pharmacological and mechanical thrombolysis with successful outcome.
    Article · Apr 2014 · Medicina
  • [Show abstract] [Hide abstract] ABSTRACT: Concurrent severe carotid and cardiac disease is a challenging situation where staged surgery is probably the most common strategy. However, in patients with an unstable clinical presentation, the best approach is still a matter of debate. To report in-hospital and midterm outcome in patients who received carotid artery stenting and synchronous cardiac surgery. From June 1998 to July 2012, 54 consecutive patients who were treated at a high-volume university medical center with this hybrid approach were included in the study. All of the patients received carotid angioplasty while being administered aspirin and regular unfractionated heparin. Then, all of the patients were immediately transferred to the operating room for coronary and/or cardiac valve surgery. All of the patients were administered aspirin and clopidogrel once bleeding was ruled out, after surgery. There were five in-hospital surgical related deaths, and no patient suffered a stroke or required carotid urgent re-intervention. At follow-up (55±28 months; range 1-144 months), there were no new neurological deficits, while one additional death occurred. In this series, synchronous carotid stenting and cardiac surgery were feasible with an acceptable complication rate in a high-surgical-risk population, which could not undergo staged procedures.
    Article · Feb 2014 · Cardiology journal
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives To report the incidence and predictors of moderate/severe radial artery spasm (RAS) in patients undergoing cardiovascular percutaneous procedures through a transradial approach (TRA) in centers with TRA expertise. Background Data regarding the actual rate of clinically meaningful RAS are limited due to difference in study designs and operator expertise. Methods The RAS registry, an international (14 centers from Argentina, Chile, India, Indonesia, Macedonia, The Netherlands and United States of America) registry that included 1,868 patients undergoing TRA cardiovascular procedures (63.5% diagnostic and 56.5% therapeutic).All selected centers used TRA as default strategy in the cardiac catheterization laboratory. Throughout 2012, each center included all consecutive TRA cases (during a 2-month period) into a dedicated database covering clinical characteristics as well as procedural topics related to TRA patterns and RAS occurrence. ResultsThe incidence of moderate/severe RAS was 2.7%. Only 0.7% of patients required crossover (8 to transfemoral and 5 to contralateral TRA). Patients with moderately/severe spasm were more frequently females, had a history of dyslipidemia, received more often a 7F sheath and more puncture attempts than patients without spasm. By multivariate analysis, the need for more than one attempt and the use of a 7 F sheath were independent predictors of the development of moderate/severe RAS. Conclusions The incidence of moderate/severe RAS is low in centers with a default TRA. Its development appears to be strongly related to the numbers of puncture attempts and the use of large sheaths. (c) 2013 Wiley Periodicals, Inc.
    Article · Jan 2014 · Catheterization and Cardiovascular Interventions
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives We aimed to assess safety and, secondarily, the efficacy of intramyocardial high-dose plasmid-vascular endothelial growth factor (VEGF) 165 (pVEGF165) gene transfer in no-option patients with coronary artery disease (CAD). Background Controlled trials of pVEGF165 in CAD have shown little benefit. One possible reason is shortness of dosage. We have shown in large mammalian models of chronic myocardial ischemia and acute myocardial infarction that intramyocardial pVEGF165 at doses significantly higher than those used in recent phase II trials is safe and efficacious on myocardial perfusion, left ventricular function, and infarct size limitation. Methods Using an injection catheter, 10 patients with severe CAD not amenable for revascularization received 10 intramyocardial injections of 0.38 mg (total dose, 3.8 mg) pVEGF165 in zones exhibiting myocardial ischemia, as assessed by combined stress 99mTc-sestamibi single-photon emission computed tomography and stress echocardiography. ResultsNo serious adverse events related to either VEGF or the injection procedure occurred over the 2-year follow-up. One patient suffered femoral artery thrombosis after a follow-up coronary angiography, successfully resolved with medical treatment. Six patients suffered uncomplicated coronary ischemic events during the second year follow-up. Angina functional class decreased from 2.6 0.2 to 1.2 +/- 0.3 (mean +/- SEM, P < 0.05), quality of life increased from 56.9 +/- 3.2 to 82.6 +/- 2.4 (P < 0.05), the summed difference score of myocardial perfusion decreased from 13.4 +/- 2 to 7.7 +/- 1.8 (P < 0.04), and stress ejection fraction did not change (44.2 +/- 3.6% to 47.8 +/- 3.1%, P = NS). Conclusions High-dose intramyocardial pVEGF165 is safe at 2 years follow-up in patients with severe CAD. The efficacy results observed must be taken cautiously given the uncontrolled, open-label study design. (c) 2012 Wiley Periodicals, Inc.
    Article · Nov 2013 · Catheterization and Cardiovascular Interventions
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    Full-text Article · Oct 2013 · Journal of the American College of Cardiology
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    Full-text Article · Oct 2013 · Journal of the American College of Cardiology
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    Full-text Article · Oct 2013 · Journal of the American College of Cardiology
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: Adipose Stromal Cells (ASCs) have been shown to display reparative and regenerative potential in diverse tissues, including skeletal muscle, mainly due to the paracrine effect of secreted angiogenic factors. On the other hand, we have demonstrated that gene transfection with a plasmid encoding human Vascular Endothelial Growth Factor (pVEGF165) promotes angio-arteriogenesis and affords protection against ischemic muscle lesions in rabbits with hind limb ischemia. We therefore hipothesised that in this animal model ASCs genetically modified to overexpress VEGF165 would exert greater anti-ischemic effect than non-modified ASCs. Methods: Rabbit ASCs were isolated, identified, cultured and transfected with pVEGF165. Rabbits with extirpation of the superficial femoral artery and ligature of the deep femoral artery of the left hind limb were randomized to receive 10 local intramuscular injections of 10 million (total amount) allogeneic modified ASCs (ASC-VEGF group, n=10), non-modified ASCs (ASC group, n=10) or PBS (placebo group, n=10). Prior to surgery, and at 1 and 30 days after treatment, Peak Systolic flow Velocity (PSV) was measured by Doppler echo in both hind limbs. At 30 days post-treatment vascular density of both hind limbs was assessed by angiography, and after euthanasia (sodium thiopental overdose followed by potassium chloride) tissue samples from the adductor, gastrocnemius and quadriceps muscles were harvested for assessment of ischemic muscle lesions. Investigators involved in data collection and analysis were blinded to the animals' study groups. Results: PSV increased in the ASC-VEGF group (pre-treatment: 11.1±3.3, post-treatment: 23.4±19 cm/sec; p<0.05, mean ± SD, 2-way ANOVA-Bonferroni), but not in the ASC (from 11±4.7 to 16±10.7 cm/sec, p=NS) or placebo (from 10.1± to 17±10.9 cm/sec p=NS) groups. In the angiography, only the ACS-VEGF group showed greater vascular density than the placebo group (5.6±1.1 vs. 4.5±0.6 vessels/cm2; p<0.04). Ischemic vascular lesions were present in 20% of the harvested samples in ASC-VEGF group, 33% in ASC group, and 73% in placebo group (p<0.05 vs. ASC-VEGF and ASC, Fisher's exact test). Conclusions: In rabbits with experimental peripheral vascular disease, the local injection of ASCs overexpressing human VEGF165 improves vascularisation and hemodinamics of the affected limb more than non-modified ASCs. However, both treatments afford protection against ischemic muscle lesions to a similar extent.
    Article · Aug 2013 · European Heart Journal
  • [Show abstract] [Hide abstract] ABSTRACT: AimTo assess the results of transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve prosthesis (Medtronic, Minneapolis, MN), without balloon predilation, in high-risk patients with degenerated severe aortic stenosis. Methods and ResultsFifty-one consecutive patients who underwent direct TAVI, 98% through a transfemoral approach. Patients were 798 years of age, 74% in New York Heart Association classes III or IV and at high risk for surgical valve replacement (mean logistic EuroScore 20 +/- 15). Mean aortic valve area was 0.7 +/- 0.2 cm(2). Procedural success rate was 94.2%. In-hospital, there were 2 deaths, 1 minor stroke with minimal sequelae, and 14 (28%) pacemaker implantation. At 30 days, there was one additional stroke and no new deaths. The mean postprocedural transprosthetic gradient was 15 +/- 5 mm Hg; periprosthetic severe regurgitation was absent and moderate in one case. After a median follow-up of 7 months, there were five additional deaths (two cardiac), while 84% of survivors were in New York Heart Association classes I or II. Conclusions These results suggest that direct CoreValve implantation in patients with severe aortic stenosis is feasible and may lead to hemodynamic and clinical improvement in patients who are poor candidates for aortic valve surgery, pending confirmation in larger series with longer follow-up. (c) 2013 Wiley Periodicals, Inc.
    Article · Aug 2013 · Catheterization and Cardiovascular Interventions
  • [Show abstract] [Hide abstract] ABSTRACT: Outcomes of Direct Implantation of Self-Expandable Aortic Valve Prosthesis for Severe Aortic Stenosis
    Article · Oct 2012
  • [Show abstract] [Hide abstract] ABSTRACT: We evaluated the incidence of clinical events after implantation of the TAXUS Liberté paclitaxel-eluting stent in saphenous vein graft (SVG) lesions in an unselected patient population. The OLYMPIA (TAXUS Liberté Post-Approval Global Registry) program gathered data on 21 954 patients receiving at least 1 TAXUS Liberté stent, including 345 patients with SVG lesions. All cardiac events were monitored with independent adjudication of end points. Patients enrolled at procedure started with no mandated inclusion/exclusion criteria. In SVG-OLYMPIA (n = 345), baseline comorbidities/complex disease were more frequent than the rest of the OLYMPIA (n = 21 560). SVG-OLYMPIA had similar cardiac death, target vessel revascularization, and definitive stent thrombosis rates than the rest of OLYMPIA. Despite higher baseline risk, the SVG-OLYMPIA had similar 12-month clinical outcome than the rest of the OLYMPIA registry, confirming the safety and efficacy of the TAXUS Liberté stent in this high-risk group.
    Article · Jan 2012 · Angiology
  • [Show abstract] [Hide abstract] ABSTRACT: La angina de pecho es un síntoma frecuente en pacientes con hipertensión pulmonar (HP) de cualquier etiología. Aunque su fisiopatología no está aclarada, las causas propuestas son: la isquemia subendocárdica por aumento del estrés parietal del ventrículo derecho, la dilatación de la arteria pulmonar por incrementos transitorios de la presión pulmonar y la compresión extrínseca del tronco de la arteria coronaria izquierda (TCI) por la arteria pulmonar (AP) dilatada. Se presentan tres casos que muestran la relación entre la angina de pecho y la compresión del TCI en pacientes con HP asociada a cardiopatías congénitas, tratados mediante implante de stent coronario.
    Article · Oct 2011 · Medicina
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    [Show abstract] [Hide abstract] ABSTRACT: Executive functions are crucial for organizing and integrating cognitive processes. While some studies have assessed the effect of carotid artery stenting (CAS) on cognitive functioning, results have been conflicting. The object of this study was to assess the effect of CAS on cognitive status, with special interest on executive functions, among patients with severe asymptomatic internal carotid artery (ICA) stenosis. The authors prospectively assessed the neuropsychological status of 20 patients with unilateral asymptomatic extracranial ICA stenosis of 60% or more by using a comprehensive assessment battery focused on executive functions before and after CAS. Individual raw scores on neuropsychological tests were converted into z scores by normalizing for age, sex, and years of education. The authors compared baseline and 3-month postoperative neuropsychological scores by using Wilcoxon signed-rank tests. The mean preoperative cognitive performance was within normal ranges on all variables. All patients underwent a successful CAS procedure. Executive function scores improved after CAS, relative to baseline performance as follows: set shifting (Trail-Making Test Part B: -0.75 ± 1.43 vs -1.2 ± 1.48, p = 0.003) and processing speed (digit symbol coding: -0.66 ± 0.85 vs -0.97 ± 0.82, p = 0.035; and symbol search: -0.24 ± 1.32 vs -0.56 ± 0.77, p = 0.049). The benefit of CAS for working memory was marginally significant (digit span backward: -0.41 ± 0.61 vs -0.58 ± 0.76, p = 0.052). Both verbal (immediate Rey Auditory Verbal Learning Test: 0.35 ± 1.04 vs -0.22 ± 0.82, p = 0.011) and visual (delayed Rey-Osterrieth Complex Figure: 0.27 ± 1.26 vs -0.22 ± 1.01, p = 0.024) memory improved after CAS. The authors found a beneficial effect on executive function and memory 3 months after CAS among their prospective cohort of consecutive patients with unilateral and asymptomatic ICA stenosis of 60% or more.
    Full-text Article · Sep 2011 · Journal of Neurosurgery
  • Oscar A Mendiz · Alberto H Sampaolesi · Hugo F Londero · [...] · Leon R Valdivieso
    [Show abstract] [Hide abstract] ABSTRACT: We report our experience using transradial access (TRA) for carotid artery stenting (CAS). Eighty-eight patients underwent CAS using a nonfemoral approach, 79 of them by TRA. Carotid artery stenting was performed using standard techniques with a long hydrophilic sheath. Mean age was 69.5 years. A total of 46 patients were symptomatic and 34 were asymptomatic. Transradial access and procedural success were achieved in 98.8% and 96.6% of the cases, respectively. There were no deaths, myocardial infarction, or radial access site complications. In all, 2 patients sustained a stroke, 1 hemorrhage, and 1 ischemia. Carotid artery stenting using TRA was safe and technically feasible.
    Article · Aug 2011 · Vascular and Endovascular Surgery
  • León Valdivieso · Miguel Cerdá · Oscar Méndiz
    Article · Jun 2011
  • Oscar A Mendiz · Carlos M Fava · León R Valdivieso · [...] · Lorena G Villagra
    [Show abstract] [Hide abstract] ABSTRACT: To report our experience in patients with critical limb ischemia (CLI) due to isolated below-the-knee (BTK) arterial lesions. Between 1992 and 2009, we performed 2747 peripheral angioplasties, while 2.8% (78 of 2747) were only BTK and were included in the present study. Mean age was 70.2 ± 11 years, 58.4% had diabetic, 85.7% were smokers, and 20.8% had chronic renal failure. Baseline Rutherford class: 50 patients with class IV and 27 with class V to VI. Angiographic and clinical success were 97.4% and 90.91%, respectively. At 30 days, there were no deaths, 2 patients had acute vessel closure and 2 major amputation. At long-term follow-up (22.4 ± 9.6 months), there were 7 unrelated deaths (10%), 5 amputations (7.1%), 3 reinterventions (4.2%), while 16 patients remained symptomatic. Overall amputation and amputation plus claudication-free survival were 90% and 70%, respectively. Endovascular treatment of BTK lesions represents a safe and effective treatment option to patients with CLI.
    Article · Mar 2011 · Angiology
  • [Show abstract] [Hide abstract] ABSTRACT: Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting.
    Article · Jan 2011 · Medicina
  • L. Valdivieso · M. Cerdá · O. Méndiz
    Article · Jan 2011
  • Oscar Mendiz · Gustavo Lev · León Valdivieso · [...] · Roberto Favaloro
    [Show abstract] [Hide abstract] ABSTRACT: Une femme diabétique de 62 ans était adressée à notre établissement avec une histoire de six mois d’hypertension pulmonaire et d’insuffisance cardiaque droite progressive. La tomodensitométrie thoracique et l’angiographie pulmonaire montraient une masse de l’artère pulmonaire. En raison de l’état précaire de la patiente, un kissing-stenting palliatif des deux artères pulmonaires était fait avec des résultats angiographiques optimaux et une amélioration clinique manifeste. Au suivi de 5 mois, les deux stents étaient perméables et une perfusion satisfaisante des poumons était observée bilatéralement.
    Article · Dec 2010 · Annales de Chirurgie Vasculaire